title: Autophagy inhibition sensitizes cisplatin cytotoxicity in human gastric cancer cell line SGC7901.
abstract: We aimed to investigate the mechanism and effects of autophagy on cisplatin (DDP)-induced apoptosis in human gastric cancer cell line SGC7901. After SGC7901 cells were treated with DDP and/or chloroquine, cell proliferation was measured using MTT assay; cell apoptosis was determined by flow cytometry; autophagy and apotosis-related proteins expression were detected by Western blot; and quantitative analysis of autophagy after monodansylcadaverine (MDC) staining was performed using fluorescence microscopy. We found after treatment with 5 mg/L DDP for 24 h, the rates of cell apoptosis were (21.07±2.12)%. Autophagy, characterized by an increase in the number of autophagic vesicles and the level of LC3-II protein was observed in cells treated with DDP. After inhibition of autophagy by chloroquine, the rates of cell apoptosis were increased to (30.16±3.54)%, and the level of Caspase-3 and P53 protein were increased, and Bcl-2 protein was decreased. Therefore, autophagy protects human gastric cancer cell line SGC7901 against DDP-induced apoptosis, inhibition of autophagy can promote apoptosis, and combination therapy with DDP and chloroquine may be a promising therapeutic strategy for gastric cancer.
authors.affiliation: The 3rd department of Medical Oncology, Jiangxi Provincial Tumor Hospital, Nanchang, China E-mail : hqzhang888@126.com, fnian3893@126.com.
authors.forename: Hui-Qing
authors.initials: HQ
authors.lastname: Zhang
authors.forename: Bo
authors.initials: B
authors.lastname: He
authors.forename: Nian
authors.initials: N
authors.lastname: Fang
authors.forename: Shan
authors.initials: S
authors.lastname: Lu
authors.forename: Yu-Qian
authors.initials: YQ
authors.lastname: Liao
authors.forename: Yi-Ye
authors.initials: YY
authors.lastname: Wan
mesh_terms: D000970:Antineoplastic Agents / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects*; D000071186:Beclin-1; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000633:toxicity*; D005434:Flow Cytometry; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D008856:Microscopy, Fluorescence; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D008565:Membrane Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D002945:Cisplatin